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Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis (UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02289417
Recruitment Status : Completed
First Posted : November 13, 2014
Results First Posted : October 29, 2018
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily [BID] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Apremilast Drug: Placebo Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Detailed Description:

Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID).

At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis
Actual Study Start Date : January 8, 2015
Actual Primary Completion Date : September 25, 2017
Actual Study Completion Date : June 3, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Apremilast

Arm Intervention/treatment
Experimental: Apremilast 30 mg PO BID

Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks

After 12 weeks:

  • Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52)
  • Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52)

After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Drug: Apremilast
Other Name: CC-10004; Otezla

Experimental: Apremilast 40 mg PO BID

Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks

After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52)

After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)

Drug: Apremilast
Other Name: CC-10004; Otezla

Placebo Comparator: Placebo BID

Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52)

After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Drug: Apremilast
Other Name: CC-10004; Otezla

Drug: Placebo



Primary Outcome Measures :
  1. Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 [ Time Frame: Week 12 ]

    Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.

    • Stool Frequency Subscore (SFS)
    • Rectal Bleeding Subscore (RBS)
    • Endoscopy Subscore
    • Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.


Secondary Outcome Measures :
  1. Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 [ Time Frame: Week 12 ]

    Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.

    • Stool Frequency Subscore (SFS)
    • Rectal Bleeding Subscore
    • Endoscopy Subscore
    • Physician's Global Assessment (PGA)

    Rectal bleeding (subscore 0-3) was defined as:

    0 = No blood seen

    1. = Streaks of blood with stool less than half the time
    2. = Obvious blood with stool
    3. = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.

  2. Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]

    An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12.

    The MES subscore findings were defined as:

    0 = Normal or inactive disease

    1. = Mild Disease (erythema, decreased vascular pattern, mild friability)
    2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)
    3. = Severe Disease (spontaneous bleeding, ulceration)

    The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.


  3. Percentage of Participants Who Achieved an Endoscopic Response at Week 12 [ Time Frame: Week 12 ]

    An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as:

    0 = Normal or inactive disease

    1. = Mild Disease (erythema, decreased vascular pattern, mild friability)
    2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration).

    The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.


  4. Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 [ Time Frame: Week 12 ]

    The RBS was measured as:

    0 = No blood seen

    1. = Streaks of blood with stool less than half the time
    2. = Obvious blood with stool most of the time
    3. = Blood alone passes

    The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.


  5. Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 [ Time Frame: Week 12 ]
    Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.

  6. Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 [ Time Frame: Week 12 ]

    Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity.

    The RBS was measured as:

    0 = No blood seen

    1. = Streaks of blood with stool less than half the time
    2. = Obvious blood with stool most of the time
    3. = Blood alone passes

    The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.


  7. Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 [ Time Frame: Week 8 ]

    Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore >1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores:

    Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

    Two-sided 95% CI for the within-group proportions are based on the Wilson score method.


  8. Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 [ Time Frame: Week 8 ]

    Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores:

    Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).

    Two-sided 95% CI for the within-group proportions are based on the Wilson score method.


  9. The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase [ Time Frame: From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks ]
    A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

  10. The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period [ Time Frame: From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks ]
    A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.

  11. The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 [ Time Frame: From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms ]
    A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

  12. The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) [ Time Frame: From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks. ]
    A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  • Male or female aged 18 and over at the time of signing the informed consent.
  • Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
  • Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit..
  • Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study.
  • Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.
  • Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  • Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
  • Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).
  • Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
  • Clinical signs suggestive of fulminant colitis or toxic megacolon.
  • Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent).
  • Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.
  • Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit.
  • Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.
  • Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
  • History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02289417


Locations
Show Show 99 study locations
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Statistical Analysis Plan  [PDF] September 29, 2017
Study Protocol  [PDF] August 8, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02289417    
Other Study ID Numbers: CC-10004-UC-001
2014-002981-64 ( EudraCT Number )
First Posted: November 13, 2014    Key Record Dates
Results First Posted: October 29, 2018
Last Update Posted: May 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: http://www.amgen.com/datasharing
Keywords provided by Amgen:
Ulcerative Colitis
Inflammatory Bowel Disease
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Apremilast
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action